ABSTRACT
Spinal gabapentin has been known to show the antinociceptive effect. Although several assumptions have been suggested, mechanisms of action of gabapentin have not been clearly established. The present study was undertaken to examine the action mechanisms of gabapentin at the spinal level. Male SD rats were prepared for intrathecal catheterization. The effect of gabapentin was assessed in the formalin test. After pretreatment with many classes of drugs, changes of effect of gabapentin were examined. General behaviors were also observed. Intrathecal gabapentin produced a suppression of the phase 2 flinching, but not phase 1 in the formalin test. The antinociceptive action of intrathecal gabapentin was reversed by intrathecal NMDA, AMPA, D-serine, CGS 15943, atropine, and naloxone. No antagonism was seen following administration of bicuculline, saclofen, prazosin, yohimbine, mecamylamine, L-leucine, dihydroergocristine, or thapsigargin. Taken together, intrathecal gabapentin attenuated only the facilitated state. At the spinal level, NMDA receptor, AMPA receptor, nonstrychnine site of NMDA receptor, adenosine receptor, muscarinic receptor, and opioid receptor may be involved in the antinociception of gabapentin, but GABA receptor, L-amino acid transporter, adrenergic receptor, nicotinic receptor, serotonin receptor, or calcium may not be involved.
Subject(s)
Animals , Male , Rats , Acetates/administration & dosage , Acetates/metabolism , Acetates/pharmacology , Adrenergic Antagonists/metabolism , Adrenergic alpha-Antagonists/metabolism , Analgesics/administration & dosage , Analgesics/metabolism , Analgesics/pharmacology , Atropine/metabolism , Dihydroergocristine/metabolism , Enzyme Inhibitors/metabolism , Excitatory Amino Acid Agonists/metabolism , GABA Antagonists/metabolism , Injections, Spinal , Leucine/metabolism , Mecamylamine/metabolism , Muscarinic Antagonists/metabolism , N-Methylaspartate/metabolism , Naloxone/metabolism , Narcotic Antagonists/metabolism , Nicotinic Antagonists/metabolism , Pain Measurement , Quinazolines/metabolism , Rats, Sprague-Dawley , Serine/metabolism , Spinal Cord/drug effects , Thapsigargin/metabolism , Triazoles/metabolism , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolismABSTRACT
Para estudiar el mecanismos de acción del AMP en el nodo A-V, se estudiaron 10 pacientes con taquicardia supraventricular por re-entrada (TVS) que incluía el nodo AV en su circuito.. El promedio de edad fue 32.8 + ou - 11.1 años. La taquicardia se indujo por estimulación auricular programada y se realizaron registros electrofisiológicos intracavitarios en todos los casos. En la primera etapa la administración de AMP suprimió la arrtmia en todos los casos en un tiempo promedio de 15.2 + ou - 2.6 seg., con una dosis de 0.095 + ou - 0.037mg/kg. En la segunda etapa la administración de atropina (0.04mg/kg.) no impidió la supresión de la arritmia. La dosis de AMP fue 0.122 + ou - 0.045mg/kg (P3NDS) y el tiempo promedio 16.2 + ou - 2.2 (p=NDS). En la tercera etapa: la administración de AMP no interrumpió la arritmia inducida bajo el efecto de atropina y aminofilina (4mg/kg) en 8 de los pacientes. En uno de los restantes la dosis necesarias fue 0.250mg/kg., y en el otro fue 0.075mg/kg. No hubo efectos colaterales graves. Se demuestra que la acción del AMP está mediada por estimulación agonista de receptores purinérgicos en el nodo AV